Synthetic Bioluminescence Allows Scientists to See Deep Tissues Using Cameras

Figure 1. Luciferase can be found on other organisms including fireflies, jellyfish, click beetles, and bacteria.

In this study, bioluminescence, the ability of a living organism to produce light, is made possible by luciferase: an enzyme derived from fireflies. The process by which luciferase catalyzes a substrate known as D-luciferin. This process generates a green-yellow glow. Atsushi Miyawaki of the RIKEN Brain Science Institute in Tokyo, in collaboration with members from the University of Electro-Communications, the Tokyo Institute of Technology, and Kyoto University, is currently using luciferase’s abilities to create bioluminescence in mammals to capture deep tissue images.

Miyawaki and his team first created a variation of luciferin that is hundreds of times stronger than the natural form. Previous research has shown that AkaLumine-HCl, a synthetic luciferin, is able to penetrate the blood-brain barrier, producing a reddish glow. This synthetic luciferin, however, is incompatible with the natural luciferin; to account for this, the researchers mutated the natural enzyme. The resulting combination, AkaBLI, produced a bioluminescence signal that is stronger than the natural signal and that can be used in vivo.

While bioluminescence can be induced in animals by simply infusing animals’ drinking water with AkaBLI, researchers were able to achieve a greater light intensity by introducing the AkaBLI via injections. When tested in mice, AkaBLI produced a bioluminescence signal 1,000 times stronger than that produced by natural luciferase-luciferin reactions. This intensity allowed scientists to track cancer cells, which may have major implications for cancer treatment research. AkaBLI even allowed researchers to track deep-brain neurons in a marmoset monkey and thereby non-invasively observe how brain activity and structures change with behavior over time; scientists were able to capture images of the tissues using light-sensitive cooled charge coupled device (CCD) cameras. Miyawaki concludes that the contributions that bioluminescence may make to scientists’ understanding of neural circuitry has extreme potential.